Breast cancer prognostic portfolio
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example 1
Producing an Optimized Portfolio
[0054]Gene expression data was recently produced from tissue samples representative of eleven different typees of cancers. The data was published in Cancer Research 61:7388-7393, 2001 and on the worldwide web of the Internet at carrier.gnf.org / welsh / epican. See Andrew 1., Su et al., “Molecular Classification of Human Carcinomas by Use of Gene Expression Signatures. ” The data included intensity measurements obtained with the use of an “U95” a ogligonucleotide microarray (commercially available from Affymetrix, Inc.)
[0055]Measurements of the expression of genes from the published data (fluorescent intensity measurements) was used to select optimum gene expression portfolios for a panel of markers to determine whether a circulating cell is indicative of the presence of breast cancer, prostate cancer, ovarian cancer, colorectal cancer, or lung cancer. Such circulating cells would preferably be epithelial cells.
[0056]The data in the study was collected fr...
example 2
Heuristic Step
[0060]A heuristic rule was further applied to the portfolio obtained in Example 1. That is, the rule stated that if the gene / marker identified would likely be expressed in peripheral blood or were well-characterized tissue markers (e.g. PSA, mammaglobin, etc.), then such genes / marker would be removed from the portfolio. Application of the rule enabled the establishment of a portfolio of genes / markers that are optimized for use in a screening application in which the patient sample is obtained by assaying components found in the peripheral blood such as epithelial cells. The result of the selected portfolio contains 31 genes as shown in Table 2.
[0061]
CancerTypeAccessionNameDescriptionSeq. ID No.PRHs.12784KIAA0293KIAA0293 proteinSeq. ID No. 67PRNM_006562LBX1transcription factor similar to D. melanogasterSeq. ID No. 33homeodomain protein lady bird latePRNM_016026LOC51109CGI-82 proteinSeq. ID No. 34PRHG2261-NoneAntigenSeq. ID No. 99HT2352PRNM_012449STEAPsix transmembrane e...
example 3
Prognostic Portfolios
[0062]A patient sample set with known clinical outcomes was used to test the portfolio selection method of the invention. The sample set is described in van't Veer, L. J et al. Gene Expression Profiling Predicts Clinical Outcome of Breast Cancer, Nature, 415, 530-536, (2002), incorporated herein by reference. In that study, breast tissue samples were obtained from 78 patients exhibiting sporadic breast tumors. The patients were all less than 55 years of age and presented with a tumor less than 5cm. All were lymph node negative. Thirty four of the patients presented with distant metastases in less than 5 years while 44 showed no distant metastases in the same period.
[0063]Sample preparation and expression profiling are described in the reference. A prognostic marker portfolio of 70 genes was selected from consideration of about 5,000 genes differentially expressed in patients with different prognoses (metastasis v. no metastasis). The selection was made based on ...
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Abstract
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